The goal of this Sequencing Core is to provide sequencing and analysis services to 3 of the Scientific Projects for a Center for Excellence in Translational Research that focuses on innovative diagnostics for childhood and drug resistant tuberculosis. The core will support the projects by using Next-Generation Sequencing to discover novel biomarkers of drug resistant in well-characterized clinical strains, to characterize mycobacterial DNA fragment that may be present in the urine of patients with active disease and to profile pools of constructed mutants that have undergone in vitro and in vivo selection under drug pressure. We will leverage our extensive previous experience in microbial whole genome sequencing and a range of custom analysis tools to ensure the technical success ofthe projects. The results of these studies will be used to lay the framework for development of a rapid and inexpensive diagnostic test that can detect the genetic signature of Mycobacteria tuberculosis and its drug resistant mutants.